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If a translocation is followed by loss of one of the two derivative chromosomes, the result is an unbalanced translocation, showing monosomy for the segments making up the lost derivative. We have found that in most unbalanced translocations, a third event takes place: a morphologically normal copy of one of the two translocation participants is added to the karyotype. This creates a complex abnormal karyotype with monosomy, disomy, and trisomy for different segments of the translocation participants. We have examined 82 unbalanced translocations from 77 patients, 73 of whom had a myeloid hemopoietic malignancy. Acquisition of a normal copy of a translocation participant was found in 49 translocations. Twenty-five of these showed trisomy for 1q. In 16 of the 25 1q-trisomic cases the translocation was t(1;7)(q10;p10) (trisomy for 1q and monosomy for 7q). Patients with trisomy for 1q were younger than the remaining patients. Whereas those with t(1;7))(q10;p10) showed brief survivals, those with trisomy 1q but monosomy for regions other than 7q survived longer than the remaining patients. We conclude that most unbalanced translocations involve a partial trisomy, that 1q is trisomic far more frequently than any other segment, and that partial trisomy is associated with patient age and survival., (Copyright 2000 Wiley-Liss, Inc.)

In a Danish population-based non-Hodgkin's lymphoma (NHL) registry (LYFO) representing a population of 2.7 million all new cases of NHL were registered from 1st January 1983 to 31st May 1994. Incidence data of primary malignant tumours of the brain and central nervous system in western Denmark for the period 1971-1990 have been obtained from the Danish Cancer Registry. During the approximate 11-year period 3124 new cases of NHL were registered. Of these, 1152 (37%) were extranodal and 48 were non-AIDS related primary central nervous system lymphomas (PCNSL) accounting for 4.2% of extranodal NHL and 1.5% of all NHL, respectively. The average annual incidence rate of non-AIDS related PCNSL during the period was 1.56 cases per million population (age range: 15-85 yrs, median: 62 yrs, M/F ratio: 1). In a 23-year period there was no trend towards an increasing incidence of non-AIDS related PCNSL in a well-defined population. PCNSL accounted for 1.7% of all primary malignant brain tumours. Incidence of primary malignant brain tumours was stable, except for age ranges over 70 years. Histologically, 85% were high grade, centroblastic diffuse (60%) and immunoblastic lymphoma (13%) (Kiel classification). No T-cell lymphomas were detected. Treatment included surgical resection, whole brain irradiation (WBRT) and chemotherapy. Median survival for those receiving either WBRT or WBRT and chemotherapy was eight months and 20 months, respectively (p = 0.78). Overall survival was 53%, 38% and 26% at one, two and five years. Cox-regression analysis identified only one factor having independent impact on survival in performance score > or = 2 (PCNSL p < 0.001, RR = 5.8).

A consecutive cohort of patients with NHL was examined to identify the factors predictive of CNS-involvement with Cox's proportional hazards model in a multivariate analysis. Twenty-seven cases of CNS-involvement were found among 498 patients with NHL. Only 3 of 96 patients with low-grade lymphomas had CNS involvement, all occurring after transformation into high-grade lymphoma. In univariate analysis of 402 patients with intermediate or high-grade lymphoma, lymphoblastic histology (including Burkitt's lymphoma), age <35 years, B-symptoms, stage IV disease, testis involvement and bone marrow involvement were found to be statistically significant risk factors. Lymphoblastic histology was found to be strongly correlated to age younger than 35 years. In the multivariate analysis only lymphoblastic histology, stage IV disease and B-symptoms were found to be significantly associated with CNS involvement. It is concluded that CNS prophylaxis should be considered in all patients with lymphoblastic histology and in patients with stage IV B lymphomas other than those of low-grade types.

It has been claimed that Primary Central Nervous System Lymphomas (PCNSL), a rare neoplasm accounting for only a small fraction of malignant brain tumors and extranodal non-Hodgkin lymphomas (NHL), occur with increasing frequency in immunologically normal as well as in immunocompromised individuals. In an attempt to characterize the clinicopathological features, outcome and prognostic factors of PCNSL we here report our experience in a large unselected series of patients from a well-defined region. In addition, we present data on trends in incidence of PCNSL and primary malignant brain tumors in a well-defined geographical area. In a Danish population-based NHL registry (LYFO) representing a population of 2.7 million all new cases of NHL were registered during the approximate 11-year period from 1st January 1983 to 31st May 1994. Incidence data of primary malignant tumors of the brain and central nervous system in western Denmark for the period 1971-1990 have been obtained from the Danish Cancer Registry. During the approximate 11-year period 3124 new cases of NHL were registered. Of these, 1152 (37%) were extranodal and 48 were non-AIDS related PCNSL accounting for 4.2% of extranodal NHL and 1.5% of all NHL, respectively. The average annual incidence rate of non-AIDS related PCNSL during the period was 1.56 cases per million population (age range: 15-85 yrs, median: 62 yrs, M/F ratio: 1). In a 23-year period there was no trend towards an increasing incidence of non-AIDS related PCNSL in a well-defined population. PCNSL accounted for 1.7% of all primary malignant brain tumors. Incidence of primary malignant brain tumors was stable, except for age ranges over 70 years. However, diagnostic artifacts might be responsible for this apparent increase. Histologically, 85% were high grade. Using the Kiel classification centroblastic diffuse (60%) and immunoblastic lymphoma (13%) were the most common subtypes. Forty-three patients had B-cell lymphoma and no T-cell lymphoma was detected. Forty-seven cases were diagnosed pre mortem. Treatment included surgical resection (26 patients), whole brain irradiation (WBRT) (43 patients) and chemotherapy (28 patients). Median survival for those receiving either WBRT or WBRT and chemotherapy was 8 months and 20 months, respectively (p = 0.78). Overall survival was 53%, 38% and 26% at 1, 2 and 5 years. Cox-regression analysis identified only one factor having independent impact on survival in PCNSL: performances score > or = 2 (p < 0.001, RR = 5.8).

Within a seven year period, 1597 newly diagnosed cases of non-Hodgkins lymphoma (NHL) were included in a Danish population-based NHL-register. Of these, 602 (38%) were aged 70 or older (age range 70-94, median: 76.8) and represented the population defined as "elderly" patients in the present study. Their average annual incidence rate was 35.7/10(5), as compared to 6.6/10(5) for patients aged < 70 (overall annual incidence: 9.5/105). Localised cases (stage I and II) and extranodal manifestations were more frequent among elderly patients. The most common sites of extranodal involvement were stomach (21% of all extranodal cases) and bone marrow (16%). Histologically, follicular centroblastic/centrocytic cases were found to be less frequent (p < 0.01) in elderly patients as compared to their younger counterparts (< 70 years), who on the other hand had a lower occurrence of diffuse centroblastic cases (p < 0.01). Overall seven year survival for the elderly patient population was 35% (median: 1.7 years), and for patients aged < 70 it was 57%. This difference persisted after correction for apparently NHL-unrelated deaths (52% vs. 66% respectively, p < 0.0001). The following poor prognostic factors for elderly patients were identified by multivariate analysis: hepatic involvement, presence of B-symptoms, high-grade histology and elevated s-LDH. The corresponding relative risk values were respectively 2.4, 2.2, 1.9 and 1.6.

The aim of this paper was to present the results of bone marrow harvest followed by cryopreservation in 22 children with various malignant diseases, and the clinical course of autologous bone marrow transplantation (ABMT) performed in 10 children (three with acute lymphoblastic leukemia (ALL), three with acute myeloblastic leukemia (AML) and four neuroblastoma stage IV (NB)). In 20/22 children the harvested bone marrow contained a sufficient number of granulocyte-macrophage-colonyforming units (GM-CFU) for later marrow reinfusion. Hematological reconstitution was obtained in all 10 children who underwent ABMT. No child died of toxicity. The median time to neutrophil count > 0.5 x 10(9)/l, thrombocyte count > 50 x 10(9)/l and to discharge from hospital were 34, 49 and 29 days respectively. Five children are alive with no evidence of active disease 11-21 months after ABMT. Five children have suffered relapse and have died. It was concluded that sufficient amounts of precursor bone marrow cells may be harvested in children during a pause in cystostatic therapy. The acute toxicity of ABMT in children with malignant diseases was only moderate.

Within a 7-year period 1,597 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) were included in a Danish population-based NHL registry. Of these, 602 (38%) were aged 70 years or older (age range 70-94, median: 76.8). They represent the population defined as 'elderly' patients in the present study. The average annual incidence rate for this elderly patient population was 35.7/10(5), as compared with 6.6/10(5) for patients aged less than 70 (overall annual incidence: 9.5/10(5)). Localised cases (stage I and II) and extranodal manifestations were found more frequently among elderly patients. The most common sites of extranodal involvement were the stomach (21% of all extranodal cases) and the bone marrow (16%). Histologically, follicular centroblastic/centrocytic cases were found to be less frequent (p less than 0.01) in elderly patients as compared to their younger counterparts (less than 70 years), who in contrast had a lower occurrence of diffuse centroblastic cases (p less than 0.01). Overall 7-year survival for the elderly patient population was 35% (median 1.7 years), and for patients aged less than 70 it was 57%. This difference persisted after correction for apparently NHL-unrelated deaths (52% vs. 66%, respectively, p less than 0.0001). Elderly patients with poor prognosis were characterised by the following features identified in a Cox-regression model: hepatic involvement, presence of B-symptoms, high-grade histology and elevated s-LDH. The corresponding relative risk values were in the order 2.4, 2.2, 1.9 and 1.6.

The authors present the organisation and preliminary experience with a comprehensive autologous bone marrow transplantation (ABMT) program in patients with malignant blood diseases. The procedure involves harvesting of bone marrow from patients in complete remission, purification of mononuclear cells and cryopreservation of these at -196 degrees C. After bone marrow cultures show that a sufficient number of hemopoietic progenitor cells (CFU-GM) are present in the marrow to reconstitute the patient, he/she is conditioned with chemo- (busulphan/cyclophosphamide (Bu + Cy)) or chemo/radiotherapy (total body radiation/cyclophosphamide (TBI + Cy)) in doses equal to those commonly used in allogeneic BMT. From February 1988 to July 1990 bone marrow (BM) was harvested from 24 patients. The median yield of mononuclear cells (MNC) was 1.2 x 10(8)/kg body weight (range 0.55-3.7). After buffy coat preparation, density gradient centrifugation, cryopreservation and thawing out, 0.60 x 10(8) MNC/kg (0.18-3.3) corresponding to 9.3 x 10(4) CFU-GM/kg (2.28-144) could be recovered. Twelve patients have received transplants, five with AML (after Bu + Cy conditioning), six with lymphoblastic lymphoma and one with Hodgkin's disease (with TBI + Cy conditioning). The median number of days to obtain greater than 1.0 x 10(9) leucocytes/l, greater than 0.5 x 10(9) neutrophils/l, greater than 50 x 10(9) thrombocytes/l and last requirement for erythrocyte transfusion were 21 (12-49), 28 (10-60), 55 (21-270) and 55 (12-129) days, respectively. Four patients had sepsis and the median duration of hospitalization was 39 (22-58) days. The most severe complications were seen in the AML patients, two of whom died during the posttransplant period (one of septicemia, one of thrombocytopenic bleeding).(ABSTRACT TRUNCATED AT 250 WORDS)

In a Danish population-based non-Hodgkin lymphoma (NHL) registry, 1257 newly diagnosed NHL cases were registered over a 5-year period. Of these, 463 (37%) were extranodal. The gastrointestinal tract was the most common site of extranodal involvement (30% of the cases). Histologically, 44% of all extranodal NHL cases had high-grade, 17% intermediate and 27% low-grade features, while 12% were unclassified. The most common histological subtype (Kiel) was the centroblastic diffuse (23% of cases). 50% of all extranodal NHL were localised (stage IE or IIE) and 27% had B symptoms. Site-specific features included a strong age-correlation for thyroid and testes lymphoma (greater than 50 years) and a high prevalence of female cases in thyroid and salivary glands lymphomas (M/F 0.14 and 0.30, respectively). Overall 7-year survival for extranodal NHL was 46% (median 4.9 years). Poor prognosis patients could be identified by the presence of one or more of the following presentation characteristics: age greater than 65 years, B symptoms, high-grade histology, disseminated disease, elevated s-IgA and hyperuricaemia. Relative risk values ranged from 2.1 for age and B symptoms to 1.7 for hyperuricaemia.

A 53-year-old woman was treated for and cured of low grade malignant lymphoma, localized to the neck, by irradiation and chemotherapy. One year later she developed signs of damage to the spinal cord with slight paraparesis of the lower extremities, which remained stationary for seven years. Then, new and rapidly progressive central and peripheral neurological symptoms developed. About one year later the patient died. At autopsy a malignant glioma of the right temporal lobe and radiation damage to the spinal cord were found. Lymphocytic infiltrations in the peripheral nerves and muscles of the lower extremities were also seen. A severe neurogenic atrophy was present but no relapse of malignant lymphoma was found. Depressed immune defense is suggested to be the cause of the pathological changes of the nervous system in this case. The inflammation of the peripheral nerves might be due to activation of a latent virus infection.

Seventeen patients with Wegener's granulomatosis are presented. The very complex clinical features are outlined. A recently suggested new classification (ELK-classification) is applied. Fourteen patients were treated with cytotoxic agents and steroids, 12 of these receiving 6-mercaptopurine. Of the ten patients still alive, eight are in remission with treatment withdrawn in three cases. The duration of the treatment is discussed. The results are largely satisfactory, but the course of the disease is still capricious. Progression to a higher step in the ELK-classification has been observed in several cases and a number of serious sequelae to the disease are recorded. The initial symptoms of Wegener's granulomatosis are varied and uncharacteristic, and it is important to bear this disease in mind when patients with a long course of apparently trivial infections or peculiar constellations of symptoms from several organs are encountered. Repeated biopsies from the respiratory tract are important in order to establish the diagnosis, but treatment should not be delayed in cases where only a tentative diagnosis can be made on the basis of a reasonably typical clinical picture, even with a negative histological response.

A 6-year-old boy presenting with swelling of cervical and axillary lymph-nodes was diagnosed as having an Epstein-Barr virus infection because of EBV-nuclear-antigen-positive B-lymphocytes in blood and lymph nodes and high antibody titres to EBV antigens. The natural killer activity of blood-lymphocytes was low, and so was the percentage of T-lymphocytes with Fc receptors for IgG (T-gamma cells). Chromosomal studies revealed a defect in the long arms of one of the chromosomes in pair no. 16 (16q22). The defect only appeared after addition of interferon to the lymphocyte cultures and preferentially in T-gamma lymphocytes. The disease progressed despite attempts to restore the patient's immune reactivity by interferon, transfer factor, and blood transfusions. Necropsy showed that the severe hyperplasia of lymph nodes found during life had become a Burkitt-like lymphoma. The possible connection between an interferon-induced chromosomal defect (break at 16q22) and reduced level of natural killer activity, reduced T-gamma lymphocytes, and proliferation of EBV-positive B-lymphocytes is discussed.

The otological manifestations of Wegener's granulomatosis were studied in 13 patients; diagnosis was confirmed histologically in 10, and in 1 patient periarteritis nodosa presented similar appearances. One patient had destruction of the external ear, and several had refractory otitis externa, usually associated with otitis media: 3 patients had serous otitis media, 4 had purulent otitis media of a fairly mild course, while 6 had otitis media of a fulminant and long-lasting course, accompanied in 5 cases by cranial nerve palsy and in 2 by widespread destruction. Most patients had major sensory hearing loss. Two had short-lasting anacusis during exacerbation of the pulmonary lesions. Often, otological manifestations were the initial signs of the disease. It is important to bear this diagnosis in mind in cases of long-lasting and atypical inflammations and in the presence of peculiar constellations of symptoms from several different organ systems.